Chapter 8: Alcohols, Ethers, and Thiols PDF

10/17/2023 ‫جامعة كل العرب‬ (2) ‫كيمياء عضوية صيدﻻنية‬ Pharmaceutical‫العرب‬ Organic ‫جامعة كل‬ Chemistry (2) ‫ مؤمن عامر‬.‫د‬...

10/17/2023 ‫جامعة كل العرب‬ (2) ‫كيمياء عضوية صيدﻻنية‬ Pharmaceutical‫العرب‬ Organic ‫جامعة كل‬ Chemistry (2) ‫ مؤمن عامر‬.‫د‬ Chapter: 8 8-1 WILLIAM H. BROWN THOMAS POON www.wiley.com/college/brown CHAPTER EIGHT Alcohols, Ethers, and Thiols Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 8-2  10/17/2023 CHAPTER 8: Alcohols, Ethers and Thiols 8.1: What Are Alcohols? 8.2: What Are the Characteristic Reactions of Alcohols? 8.3: What Are Ethers? 8.4 : What Are Epoxides? 8.5: What Are Thiols? 8.6 : What Are the Characteristic Reactions of Thiols? 8-3 CHAPTER 8: Alcohols, Alcohols Ethers and Thiols 8-4  10/17/2023 Structure 8.1: What Are Alcohols? A: Structure The functional group of an alcohol : is an -OH (hydroxyl) group bonded to an sp3 hybridized carbon. Bond angles about the hydroxyl oxygen atom are approximately 109.5°. Oxygen is also sp3 hybridized. Two sp3 hybrid orbitals form sigma bonds to carbon and hydrogen. The remaining two sp3 hybrid orbitals each contain an unshared pair of electrons. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 8-5 8.1: What Are Alcohols? Structure B: Numenclature IUPAC names: 1. The parent chain is the longest chain that contains the -OH group. 2. Number the parent chain in the direction that gives the -OH group. the lower number. 3. Change the suffix -e to -ol. Common names: Name the alkyl group bonded to oxygen followed by the word alcohol. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 8-6  10/17/2023 Structure 8.1: What Are Alcohols? B: Numenclature Examples: Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 8-7 8.1: What Are Alcohols? Structure B: Numenclature Name cyclic alcohols? Textbook Page 241 1. Determine the root name of the cycloalkane, and replace the suffix –e with -ol. 2. Number the substituents. Numbering begins at the carbon bearing the -OH group and proceeds in the direction that gives the lowest total for all substituents with -ol. 3. Name the structure placing substituents in alphabetical order preceded by its position on the ring. 4. Don’t forget to indicate stereochemistry. 8-8  10/17/2023 Structure 8.1: What Are Alcohols? B: Numenclature Example 8.1 page 241: Write the IUPAC name for each alcohol: Problem 8.1 page 242: Write the IUPAC name for each alcohol: 8-9 8.1: What Are Alcohols? Structure B: Numenclature We classify alcohols as primary (1°), secondary (2°), or tertiary (3°), depending on whether the -OH group is on a primary, secondary, or tertiary carbon. Example 8.2 page 242: Classify each alcohol as primary, secondary, or tertiary: Problem 8.2 page 242: Classify each alcohol as primary, secondary, or tertiary: 8-10  10/17/2023 Structure 8.1: What Are Alcohols? B: Numenclature Compounds containing : two -OH groups are named as diols, three -OH groups are named as triols and so on. In IUPAC names for diols and triols, and so on,the final -e of the parent alkane name is retained, as for example, in 1,2-ethanediol. -OH groups on adjacent carbons are called glycols. 8-11 8.1: What Are Alcohols? Structure B: Numenclature Unsaturated alcohols: The double bond is shown by the infix -en-. The hydroxyl group is shown by the suffix -ol. Number the chain to give OH the lower number. example 8-12  10/17/2023 Structure 8.1: What Are Alcohols? B: Numenclature Example 8.3 page 244: Write the IUPAC name for each alcohol: Problem 8.3 page 244: Write the IUPAC name for each alcohol: 8-13 8.1: What Are Alcohols? Structure C: Physical properties: The most important physical property of alcohols is the polarity of their -OH groups. Because of the large difference in electronegativity between O and C (3.5 - 2.5 = 1.0) and between O and H (3.5 - 2.1 = 1.4), both the C-O and O-H bonds of an alcohol are polar covalent, and alcohols are polar molecules Figure 8.2 for methanol. 8-14  10/17/2023 Structure 8.1: What Are Alcohols? C: Physical properties: Alcohols associate in the liquid state by hydrogen bonding. Hydrogen bonding: The attractive force between a partial positive charge on hydrogen and a partial negative charge on a nearby oxygen, nitrogen, or fluorine atom. Figure 8.3 ethanol molecule: 8-15 8.1: What Are Alcohols? Structure C: Physical properties: Alcohols associate in the liquid state by hydrogen bonding. Hydrogen bonding: The attractive force between a partial positive charge on hydrogen and a partial negative charge on a nearby oxygen, nitrogen, or fluorine atom. The strength of hydrogen bonding in alcohols is approximately 2 to 5 kcal/mol. Hydrogen bonds (O---H) are considerably weaker than covalent bonds O-H (~110 kcal/mol for an O–H bond). Nonetheless, hydrogen bonding can have a significant effect on physical properties. 8-16  10/17/2023 Structure 8.1: What Are Alcohols? C: Physical properties: 8-17 8.1: What Are Alcohols? Structure C: Physical properties: Boiling point: Because of hydrogen bonding between alcohol molecules in the liquid state, extra energy is required to separate each hydrogen- bonded alcohol molecule from its neighbors—hence the relatively high boiling points of alcohols compared with those of alkanes. The presence of additional hydroxyl groups in a molecule further increases the extent of hydrogen bonding. Because of increased dispersion forces between larger molecules, boiling points of all types of compounds, including 8-18 alcohols, increase with increasing molecular weight.  10/17/2023 Structure 8.1: What Are Alcohols? C: Physical properties: 8-19 8.1: What Are Alcohols? Structure C: Physical properties: Solubility in Water: Alcohols are much more soluble in water than are alkanes, alkenes, and alkynes of comparable molecular weight. Their increased solubility is due to hydrogen bonding between alcohol molecules and water. Methanol, ethanol, and 1-propanol are soluble in water in all proportions. As molecular weight increases, the physical properties of alcohols become more like those of hydrocarbons with comparable molecular weight. Alcohols with higher molecular weight are much less soluble in water because of the increase in size of the hydrocarbon portion of 8-20 their molecules.  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? A: Acidity of Alcohols: Most alcohols are about the same or slightly weaker acids than water. 8-21 8.2: What Are the Characteristic Reactions of Alcohols? Structure B: Basicity of Alcohols: In the presence of strong acids, the oxygen atom of an alcohol behaves as a weak base. Proton transfer from the strong acid forms an oxonium ion. Thus, alcohols can function as both weak acids and weak bases 8-22  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? C: Reaction with Active Metals: Alcohols react with Li, Na, K, and other active metals to liberate hydrogen gas and form metal alkoxides. Na is oxidized to Na+ and H+ is reduced to H2. Alkoxides are somewhat stronger bases that OH–. Alkoxides can be used as nucleophiles in nucleophilic substitution reactions. They can also be used as bases in -elimination reactions.8-23 8.2: What Are the Characteristic Reactions of Alcohols? Structure C: Reaction with Active Metals: Example 8.4 page 248: Write balanced equations for the following reactions. If the reaction is an acid–base reaction, predict its position of equilibrium. Problem 8.4 page 249: Write balanced equations for the following reactions….. 8-24  10/17/2023 2.3: How Do We Measure the Strength of an Acid Electronic Structure of Atoms or Base? Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. 8-25 8.2: What Are the Characteristic Reactions of Alcohols? Structure D: Conversion to Haloalkanes: Water-soluble 3° alcohols react very rapidly with HCl(aq), HBr(aq), and HI(aq). Low-molecular-weight water soluble 1° and 2° alcohols are unreactive under these conditions. 8-26  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? D: Conversion to Haloalkanes: Water-insoluble 3° alcohols react by bubbling gaseous HCl through a solution of the alcohol dissolved in diethyl ether or THF. Water-insoluble primary and secondary alcohols react only slowly under these conditions. 8-27 8.2: What Are the Characteristic Reactions of Alcohols? Structure D: Conversion to Haloalkanes: 1° and 2° alcohols require concentrated HBr and HI to form alkyl bromides and iodides. On the basis of observations of the relative ease of reaction of alcohols with HX (3° > 2° > 1°), it has been proposed that the conversion of tertiary and secondary alcohols to haloalkanes by concentrated HX occurs by an SN1 mechanism. 8-28 Primary alcohols react with HX by an SN2 mechanism.  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? D: Conversion to Haloalkanes: 3° Alcohols react with HX by an SN1 mechanism. Mechanism: Reaction of 3° Alcohol with HCl: An SN1 Reaction: Step 1: Add proton 8-29 8.2: What Are the Characteristic Reactions of Alcohols? Structure D: Conversion to Haloalkanes: Step 2: Break a bond to form a stable molecule or ion. Step 3: Reaction of an electrophile and a nucleophile to form a new covalent bond 8-30  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? D: Conversion to Haloalkanes: 1° alcohols react with HX by an SN2 mechanism. Mechanism: Reaction of 1° Alcohol with HBr: An SN2 Reaction: Step 1: Add proton 8-31 8.2: What Are the Characteristic Reactions of Alcohols? Structure D: Conversion to Haloalkanes: Step 2: Reaction of an electrophile and a nucleophile to form a new covalent bond and break a bond to form a stable molecule or ion. 8-32  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? D: Conversion to Haloalkanes: Why do 3° alcohols react with HX by formation of carbocation intermediates, whereas 1° alcohols react by direct displacement of –OH (more accurately, by displacement of -OH2+)? The answer is a combination of the same two factors involved in nucleophilic substitution reactions of haloalkanes 1. Electronic factors Tertiary carbocations are the most stable whereas primary carbocations are the least stable. 2. Steric factors: the relative ease of approach of the nucleophile to the site of reaction. Relative rates: methyl > 1° > 2° > 3° 8-33 Structure 8-34  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? D: Conversion to Haloalkanes: Thionyl chloride, SOCl2, is the most widely used reagent for conversion of primary and secondary alcohols alcohols to alkyl chlorides. 8-35 8.2: What Are the Characteristic Reactions of Alcohols? Structure E: Acid –Catalyzed Dehaydration to Alkene An alcohol can be converted to an alkene by dehydration that is by the elimination of H and OH (water) from adjacent carbons (a -elimination). 1° alcohols must be heated at high temperature in the presence of an acid catalyst, such as H2SO4 or H3PO4. 2° alcohols undergo dehydration at somewhat lower temperatures. 3° alcohols often require temperatures at or only slightly above room temperature. 8-36  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? E: Acid –Catalyzed Dehaydration to Alkene Examples: 8-37 8.2: What Are the Characteristic Reactions of Alcohols? Structure E: Acid –Catalyzed Dehaydration to Alkene When isomeric alkenes are obtained, the more stable alkene (the one with the greater number of substituents on the double bond) generally predominates (Zaitsev’s rule). 8-38  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? E: Acid –Catalyzed Dehaydration to Alkene Acid–Catalyzed Dehaydration of 2° and 3° alcohol occurrs by a E1 mechanism. Mechanism: Acid-Catalyzed Dehydration of 2-Butanol: An E1 Mechanism Step 1: Add proton 8-39 8.2: What Are the Characteristic Reactions of Alcohols? Structure E: Acid –Catalyzed Dehaydration to Alkene Step 2: Break a bond to form a stable molecule or ion. Step 3: Take away a proton 8-40  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? E: Acid –Catalyzed Dehaydration to Alkene Acid–Catalyzed Dehaydration of 1° alcohol occurrs by a E2 mechanism. Mechanism: Acid-Catalyzed Dehydration of Ethanol: An E2 Mechanism Step 1: Add proton 8-41 8.2: What Are the Characteristic Reactions of Alcohols? Structure E: Acid –Catalyzed Dehaydration to Alkene Step 3: Take away a proton and break a bond to form a stable molecule or ion. 8-42  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? E: Acid –Catalyzed Dehaydration to Alkene Acid-catalyzed hydration of an alkene and Acid-catalyzed dehydration of an alcohol are competing processes. Large amounts of water favor alcohol formation. Scarcity of water or experimental conditions where water is removed favor alkene formation. 8-43 8.2: What Are the Characteristic Reactions of Alcohols? Structure E: Acid –Catalyzed Dehaydration to Alkene Example 8.5 page 256: For each of the following alcohols, draw structural formulas for the alkenes that form upon acid- catalyzed dehydration, and predict which alkene is the major product from each alcohol. Be aware that rearrangements may occur because carbocations are formed in the reactions. 8-44  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? E: Acid –Catalyzed Dehaydration to Alkene Problem 8.5 page 256: For each of the following alcohols, draw structural formulas for the alkenes that form upon acid- catalyzed dehydration, and predict which alkene is the major product: 8-45 8.2: What Are the Characteristic Reactions of Alcohols? Structure F: Oxidation of Primary and Secondary Alcohols Oxidation of a 1° alcohol gives an aldehyde or a carboxylic acid, depending on the oxidizing agent and experimental conditions. Chromic acid, H2CrO4, oxidation of 1-octanol gives octanoic acid. 8-46  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? F: Oxidation of Primary and Secondary Alcohols PCC is used To oxidize a 1° alcohol to an aldehyde. PCC oxidation of geraniol gives geranial. 8-47 8.2: What Are the Characteristic Reactions of Alcohols? Structure F: Oxidation of Primary and Secondary Alcohols Oxidation of a 2° alcohol gives a ketone. 2° alcohols are oxidized to ketones by both chromic acid and PCC: 8-48  10/17/2023 Structure 8.2: What Are the Characteristic Reactions of Alcohols? F: Oxidation of Primary and Secondary Alcohols Tertiary alcohols are not oxidized by either of these reagents; they are resistant to oxidation. Note that the essential feature of the oxidation of an alcohol is the presence of at least one hydrogen on the carbon bearing the OH group. 8-49 8.3: What Are Ethers? Structure A: Structure: The functional group of an ether is an oxygen atom bonded to two carbon atoms. Oxygen is sp3 hybridized with bond angles of approximately 109.5°. In dimethyl ether, the C–O–C bond angle is 110.3°. 8-50  10/17/2023 Structure 8.3: What Are Ethers? B: Nomenclature: IUPAC: The longest carbon chain is the parent alkane. Name the -OR group as an alkoxy substituent. Common names: Name the groups bonded to oxygen followed by the word ether. 8-51 8.3: What Are Ethers? Structure B: Nomenclature: In ethyl vinyl ether, the ether oxygen is bonded to one sp3 hybridized carbon and one sp2 hybridized carbon: Cyclic ethers: Cyclic ethers: are heterocyclic compounds in which the ether oxygen is one of the atoms in a ring. Although cyclic ethers have IUPAC names, their common names are more widely used. 8-52  10/17/2023 Structure 8.3: What Are Ethers? B: Nomenclature: Example 8.7 page 261: Write the IUPAC and common names for each ether: Problem 8.7 page 261: Write the IUPAC and common names for each ether: 8-53 8.3: What Are Ethers? Structure C: Physical Properties Ethers are polar molecules in which each C-O bond is polar covalent. Because of steric hindrance, only weak attractive forces exist between ether molecules in the pure liquid, as shown in figure 8.5 8-54  10/17/2023 Structure 8.3: What Are Ethers? C: Physical Properties Boiling point: Because of the weak attractive forces exist between ether molecules, boiling points of ethers are much lower than those of alcohols of comparable molecular weight (Table 8.3). 8-55 8.3: What Are Ethers? Structure C: Physical Properties For example: the boiling points of ethanol (78 °C) and its constitutional isomer dimethyl ether (-24 °C). The difference in boiling points between these two compounds is due to the polar O-H group in the alcohol, which is capable of forming intermolecular hydrogen bonds. This hydrogen bonding increases the attractive force between molecules of ethanol; thus, ethanol has a higher boiling point than dimethyl ether. Boiling points of ethers are close to those of hydrocarbons of comparable molecular weight. 8-56  10/17/2023 Structure 8.3: What Are Ethers? C: Physical Properties: Boiling point: Because of the weak attractive forces exist between ether molecules, boiling points of ethers are much lower than those of alcohols of comparable molecular weight (Table 8.3). 8-57 8.3: What Are Ethers? Structure C: Physical Properties Solubility in Water: Ethers form hydrogen bonds with water (Figure 8.6) and are more soluble in water than are hydrocarbons of comparable molecular weight and shape (Table 8.3). Figure 8.6 Ethers are hydrogen bond cceptors only. They are not hydrogen 8-58 bond donors.  10/17/2023 Structure 8.3: What Are Ethers? C: Physical Properties Example 8.8 page 263: Arrange these compounds in order of increasing solubility in water: Problem 8.8 page 263: Arrange these compounds in order of increasing boiling point: 8-59 8.3: What Are Ethers? Structure D: Reaction of Ethers: Ethers resemble hydrocarbons in their resistance to chemical reaction. They do not react with strong oxidizing agents such as chromic acid, H2CrO4. They are not affected by most acids and bases at moderate temperatures. Because of their good solvent properties and general inertness to chemical reaction, ethers are excellent solvents in which to carry out organic reactions. 8-60  10/17/2023 Structure 8.4: What Are Epoxides? A: structure and Nomenclature: Epoxide: A cyclic ether in which oxygen is one atom of a three- membered ring. B: Synthesis from Alkenes: Ethylene oxide is synthesized from ethylene and O2. 8-61 Structure 8.4: What Are Epoxides? B: Synthesis from Alkenes: Other epoxides can be synthesized from an alkene by oxidation with a peroxycarboxylic acid, RCO3H. 8-62  10/17/2023 8.4: What Are Epoxides? Structure B: Synthesis from Alkenes: The epoxidation of an alkene is stereoselective. Textbook page 265 8-63 Structure 8.4: What Are Epoxides? B: Synthesis from Alkenes: Example 8.9 page 265: Draw a structural formula of the epoxide formed by treating trans-2-butene with a peroxycarboxylic acid. Problem 8.9 page 265: Draw the structural formula of the epoxide formed by treating 1,2-dimethylcyclopentene with a peroxycarboxylic acid. 8-64  10/17/2023 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: Ethers are generally unreactive to aqueous acid. Because of the angle strain in the three-membered ring, Epoxides react readily and undergo ring-opening reactions with a variety of nucleophilic reagents. Reaction of an Ethylene epoxide with aqueous acid gives a glycol. 8-65 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: The acid-catalyzed ring opening of epoxides shows a stereoselectivity typical of SN2 reactions: The nucleophile attacks anti to the leaving hydroxyl group, and the –OH groups in the glycol thus formed are anti. As a result, the acid-catalyzed hydrolysis of an epoxycycloalkane yields a trans-1,2-cycloalkanediol: 8-66  10/17/2023 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: The Mechanism of acid-catalyzed hydrolysis of an epoxide involves three steps. Step 1: Add a proton Step 2: Reaction of an electrophile and a nucleophile to form a new covalent bond. Step 3: Take away a proton. 8-67 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: Example 8.10 page 266: Draw the structural formula of the product formed by treating cyclohexene oxide with aqueous acid. Be certain to show the stereochemistry of the product. Problem 8.10 page 267: Show how to convert 1,2- dimethylcyclohexene to trans-1,2-dimethylcyclohexane-1,2-diol. 8-68  10/17/2023 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: Ethers does not react with electrophiles and poor nucleophiles such as H2O, ROH.(it is possible with acid-catalyst). Epoxides undergo ring-opening reactions, as we learn, with good and moderate nucleophiles such as ammonia, amines, alkoxide ions, and thiols and their anions. Good and moderate nucleophiles attack the ring by an SN2 mechanism and show a stereoselectivity for attack of the nucleophile at the less hindered carbon of the three- membered ring. 8-69 8.4: What Are Epoxides? Structure C: Ring-Opening Reactions: 8-70  10/17/2023 Structure 8.4: What Are Epoxides? C: Ring-Opening Reactions: Following are structural formulas for two common drugs, each synthesized in part with ethylene oxide as a building block. Novocaine was the first injectable local anesthetic. Benadryl was the first synthetic antihistamine. 8-71 Structure 8.5: What Are Thiols? A: Structure: The functional group of a thiol is an -SH group bonded to an sp3 hybridized carbon. The most outstanding property of low-molecular-weight thiols is their stench. They are responsible for the unpleasant odors such as those from skunks, rotten eggs, and sewage Figure 8.7: Methanethiol. The electronegativities of carbon and sulfur are virtually identical (2.5 each), while sulfur is slightly more electronegative8-72 than hydrogen (2.5 vurses 2.1)  10/17/2023 Structure 8.5: What Are Thiols? B: Nomenclature: IUPAC names: 1. The parent chain is the longest chain containing the -SH group. 2. Add -thiol to the name of the parent chain. Common names Name the alkyl group bonded to sulfur followed by the word mercaptan. Alternatively, indicate the -SH by the prefix mercapto. 8-73 Structure 8.5: What Are Thiols? B: Nomenclature: Sulfur analogs of ethers (thioether) are named by using the word sulfide to show the presence of the –S– group. Following are common names of two sulfides: 8-74  10/17/2023 Structure 8.5: What Are Thiols? B: Nomenclature: Example 8.11 page 270: Write the IUPAC name for each compound: Problem 8.11 page 270: Write the IUPAC name for each thiol:. 8-75 Structure 8.5: What Are Thiols? C: Physical Properties: The difference in electronegativity between S and H is 2.5 – 2.1 = 0.4 and no difference in electronegativity between S and C. Therefore, Thiols are non polar molecules does not show association by hydrogen bonding. Thiol, have lower boiling points and are less soluble in water than alcohols of comparable number of carbon atoms. 8-76  10/17/2023 Structure 8.5: What Are Thiols? C: Physical Properties: The boiling points of thiols and their constitutional isomers are almost identical. For example 8-77 Structure 8.6: What Are the Characteristic Reactions of Thiols? A: Acidity: Thiols are stronger acids than alcohols. Thiols react with strong bases to form salts. 8-78